This application proposes to determine the feasibility of developing and mass producing a continuous electrochemical sensor suitable for in vivo glucose monitoring and implantation. The sensor will be comprised of a hydrogen peroxide electrode in concert with an immobilized glucose oxidase membrane. Research support is requested to further develop and optimize both the electrode and membrane components. Historically, continuous glucose enzyme electrodes show linearity, drift, and flow sensitivity problems, particularly in the physiological environment. Our research has shown that this is due to oxygen depletion within the membrane, with digital simulations providing prediction of the required glucose/oxygen permeability properties which minimize this problem. This knowledge made possible Direct 30/30, the first reusable electrochemical sensor for home glucose monitoring. This application proposes modification of the Direct 30/30 technology to allow in vivo glucose monitoring. Systematic membrane composition variations will be performed to tune-in this application's required Permeability window. This additional membrane research, with appropriate electrode geometry and miniaturization, should produce an implantable subcutaneous glucose electrode suitable for long-term monitoring. Phase I will be used to perform the material screen and to build and evaluate the prototype electrodes. Phases II and III will be directed towards sensor clinical validation and mass production.